4-((4-hydroxy-2-methoxy-3,5,6-trimethylbenzoyl)oxy)-2-methoxy-3,5,6-trimethylbenzoic acid | 148014-39-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 4-((4-hydroxy-2-methoxy-3,5,6-trimethylbenzoyl)oxy)-2-methoxy-3,5,6-trimethylbenzoic acid
• 英文别名: 4-(4-Hydroxy-2-methoxy-3,5,6-trimethylbenzoyl)oxy-2-methoxy-3,5,6-trimethylbenzoic acid
• CAS: 148014-39-5
• 化学式: C₂₂H₂₆O₇
• 分子量: 402.444
• InChiKey: MUQKNNNEHVXLOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-((4-hydroxy-2-methoxy-3,5,6-trimethylbenzoyl)oxy)-2-methoxy-3,5,6-trimethylbenzoic acid 在 正丁基锂 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 生成 Isophthalic acid bis-[4-(4-benzhydryloxycarbonyl-3-methoxy-2,5,6-trimethyl-phenoxycarbonyl)-3-methoxy-2,5,6-trimethyl-phenyl] ester
  参考文献：
  名称：

  Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives

  摘要：

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.

  DOI：

  10.1021/jm960437a
• 作为产物：
  描述：

  梭孢壳素B 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.0h， 以19.3 mg的产率得到4-((4-hydroxy-2-methoxy-3,5,6-trimethylbenzoyl)oxy)-2-methoxy-3,5,6-trimethylbenzoic acid
  参考文献：
  名称：

  Thielavins as Glucose-6-phosphatase (G6Pase) Inhibitors: Producing Strain, Fermentation, Isolation, Structural Elucidation and Biological Activities.

  摘要：

  使用大鼠肝微粒体葡萄糖-6-磷酸酶（G6Pase）对微生物提取物进行高通量筛选，我们发现thielavin B是一种G6Pase抑制剂，可抑制胰高血糖素刺激肝细胞产生的葡萄糖。进一步寻找更有效的类似物，除了已知来自真菌Chaetomium carinthiacum ATCC 46463的thielavin A和B外，还发现了11种新的thielavin F-P。Thielavin G作为G6Pase抑制剂表现出最强的活性（IC50=0.33μM），而thielavin B的IC50为5.5μM。根据结构活性关系，包括真正的thielavin C、D和来自thielavin A和B的3个部分水解产物，3个苯甲酸单元和羧酸功能对于G6Pase抑制至关重要。

  DOI：

  10.7164/antibiotics.55.941

文献信息

• Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer
  作者：Kosuke Ohsawa、Masahito Yoshida、Miho Izumikawa、Motoki Takagi、Kazuo Shin-ya、Naoki Goshima、Takatsugu Hirokawa、Tohru Natsume、Takayuki Doi

  DOI：10.1016/j.bmc.2018.11.001

  日期：2018.12

  The synthesis and biological evaluation of thielocin B1 analogues have been demonstrated. Fourteen analogues modified in the central core and terminal carboxylic acid moiety were concisely synthesized by simple esterification or etherification reaction. The evaluation of synthetic analogues as inhibitors of proteasome assembling chaperone (PAC) complexes (the PAC3 homodimer and PAC1/PAC2) revealed

  Thielocin B1类似物的合成和生物学评估已得到证实。通过简单的酯化或醚化反应简明地合成了在中心核和末端羧酸部分中修饰的十四个类似物。对作为蛋白酶体组装伴侣（PAC）复合物（PAC3同型二聚体和PAC1 / PAC2）抑制剂的合成类似物的评估表明，类似天然产物的弯曲结构和末端羧酸基团对其生物学活性至关重要。此外，SAR和计算机对接研究表明，Thielocin B1的二苯醚部分上的所有甲基均通过疏水作用对PAC3同型二聚体产生有效和选择性的抑制作用。